Kv10.1 potassium channels in cancer

Published on November 30, 2023   30 min

A selection of talks on Cell Biology

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Hello. This is a talk recorded on behalf of Luis Pardo, a scientist at the Max Planck Institute for Multidisciplinary Sciences in Göttingen, Germany. An institute focusing mainly on neuroscience and universal neuroscience research. Doctor Pardo and his team discovered that voltage gated potassium channels are relevant for cancer, and that is the focus of today's talk. The title of the talk is K_v 10.1 potassium channels in cancer. Which is an expansion and an update of an older talk recorded approximately 10 years ago.
The main feature highlighted today is that K_v 10.1 is a bona fide voltage gated potassium channel expressing neurons. It opens in response to membrane potential depolarization and decreases neuronal excitability. It is abundantly expressed in the human brain, but it is not detectable in non neural tissues. From a pathological point of view, there are genetic diseases that imply a gain of function, mutation of the channel, and result in problems in the development and a different neurological phenotype with different forms of epilepsy. But what's relevant for the talk today is that the channel, although it is a brain potassium channel, is very frequently expressed in tumor tissues. When it is expressed in tumor tissues, it provides the tumor cells with a selective advantage in such a way that at the end of the evolution of a tumor, you typically see a very homogeneous expression in the vast majority of tumor cells. Since it is so abundantly expressed and normally it is not expressed in the tissue where the tumor originated, The potassium channel has potential as a therapeutic target.
The next slide summarizes the evidence that K_v 10.1 is abundantly expressed in the brain. In the left part of the slide, you can see a real time PCR and the mRNA expression in different tissues of humans. If you normalize and set the value of expression in the brain to one, you can see that there is a little bit of expression maybe in the spinal cord, which could even be contaminated by higher level tissues, but it is essentially absent from all other normal tissues. Then on the right side, there is a table with a series of determinations of the expressions of K_v 10.1 protein. There is some immunohistochemistry in clinical tumors from different origins, from biobanks and clinics that has been done by Dr. Pardo's lab in the majority of the cases. It has also been done in other laboratories which confirmed the finding that over 70% of all human carcinomas and sarcomas express K_v 10.1 The only cancer that has low expression of the channel in studies is chronic leukemia.